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BRG1 regulation by miR-155 in human leukemia and lymphoma cell lines

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Clinical and Translational Oncology Aims and scope Submit manuscript

An Expression of Concern to this article was published on 26 July 2019

A Correction to this article was published on 26 July 2019

This article has been updated

Abstract

Introduction/purpose

BRG1 is a key regulator of leukemia stem cells. Indeed, it has been observed that this type of cells is unable to divide, survive and develop new tumors when BRG1 is down-regulated.

Materials and methods

We assessed BRG1 and miR-155 expression in 23 leukemia cell lines, and two no pathological lymphocyte samples using qPCR. MiR-155 transfection and western blot were used to analyze the relationship between miR-155 and its validated target, BRG1, by measuring protein expression levels. The effect of miR-155 on cell proliferation and prednisolone sensitivity were studied with resazurin assay.

Results

BRG1 expression levels could correlate negatively with miR-155 expression levels, at least in Burkitt’s lymphoma and diffuse large B cell lymphoma (DLBCL) cell lines. To clarify the role of miR-155 in the regulation of BRG1 expression, we administrated miR-155 mimics in different leukemia/lymphoma cell lines. Our results suggest that miR-155 regulate negatively and significantly the BRG1 expression at least in the MOLT4 cell line.

Conclusion

Our study revealed a previously unknown miR-155 heterogeneity that could result in differences in the treatment with miRNAs in our attempt to inhibit BRG1. However, the expression levels of BRG1 and miR-155, before prednisolone treatment were not statistically significantly associated prednisolone sensitive leukemia cells.

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Change history

  • 26 July 2019

    Upon publication, it came to our attention that certain revisions were necessary to honor the agreement between University of Hawaii and APEC Climate Center for the project, ���Development of APCC Seamless Prediction System���. There are three sections that are to be corrected to accurately reflect the agreement of project.

  • 26 July 2019

    Upon publication, it came to our attention that certain revisions were necessary to honor the agreement between University of Hawaii and APEC Climate Center for the project, ���Development of APCC Seamless Prediction System���. There are three sections that are to be corrected to accurately reflect the agreement of project.

References

  1. Wilson BG, Roberts CWM. SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer. 2011;11:481–92.

    Article  CAS  Google Scholar 

  2. Sentani K, Oue N, Kondo H, Kuraoka K, Motoshita J, Ito R, et al. Increased expression but not genetic alteration of BRG1, a component of the SWI/SNF complex, is associated with the advanced stage of human gastric carcinomas. Pathobiology. 2001;69:315–20.

    Article  CAS  Google Scholar 

  3. Al Sun, Tawfik O, Gayed B, Thrasher JB, Hoestje S, Li C, et al. Aberrant expression of SWI/SNF catalytic subunits BRG1/BRM is associated with tumor development and increased invasiveness in prostate cancers. Prostate. 2007;67:203–13.

    Article  Google Scholar 

  4. Lin Hl, Wong RP, Martinka M, Li G. BRG1 expression is increased in human cutaneous melanoma. Br J Dermatol. 2010;163:502–10.

    Article  CAS  Google Scholar 

  5. Song S, Walter V, Karaca M, Li Y, Bartlett CS, Smiraglia DJ, et al. Gene silencing associated with SWI/SNF complex loss during NSCLC development. Mol Cancer Res. 2014;12:560–70.

    Article  CAS  Google Scholar 

  6. Buscarlet Manuel, Krasteva Veneta, Ho Lena, Simon Camille, Hébert Josée, Wilhelm Brian, et al. Essential role of BRG, the ATPase subunit of BAF chromatin remodeling complexes, in leukemia maintenance. Blood. 2014;123:1720–8.

    Article  CAS  Google Scholar 

  7. Shi J, Whyte WA, Zepeda-Mendoza CJ, Milazzo JP, Shen C, Roe J, et al. Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated MYC regulation. Genes Dev. 2013;27:2648–62.

    Article  CAS  Google Scholar 

  8. Pottier N, Yang W, Assem M, Panetta JC, Pei D, Paugh SW, et al. The SWI/SNF chromatin-remodeling complex and glucocorticoid resistance in acute lymphoblastic leukemia. J Natl Cancer Inst. 2008;100:1792–803.

    Article  CAS  Google Scholar 

  9. Rajewsky N. microRNA target predictions in animals. Nat Genet. 2006;38(Suppl):S8–13.

    Article  CAS  Google Scholar 

  10. Takada S, Yamashita Y, Berezikov E, Hatanaka H, Fujiwara S, Kurashina K, et al. MicroRNA expression profiles of human leukemias. Leukemia. 2008;22:1274–8.

    Article  CAS  Google Scholar 

  11. Dunand-Sauthier I, Santiago-Raber ML, Capponi L, Vejnar CE, Schaad O, Irla M, et al. Silencing of c-Fos expression by microRNA-155 is critical for dendritic cell maturation and function. Blood. 2011;117:4490–500.

    Article  CAS  Google Scholar 

  12. Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, et al. Requirement of bic/microRNA-155 for normal immune function. Science. 2007;316:608–11.

    Article  CAS  Google Scholar 

  13. Thai TH, Calado DP, Casola S, Ansel KM, Xiao C. Xue Yet al. Regulation of the germinal center response by microRNA-155. Science. 2007;316:604–8.

    Article  CAS  Google Scholar 

  14. Eis PS, Tam W, Sun L, Chadburn A, Li Z, Gomez MF, et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci USA. 2005;102:3627–32.

    Article  CAS  Google Scholar 

  15. Kluiver J, Poppema S, de Jong D, Blokzijl T, Harms G, Jacobs S, et al. BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas. J Pathol. 2005;207:243–9.

    Article  CAS  Google Scholar 

  16. Kadoch C, Hargreaves DC, Hodges C, Elias L, Ho L, Ranish J, et al. Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat Genet. 2013;45:592–601.

    Article  CAS  Google Scholar 

  17. Romero OA, Torres-Diz M, Pros E, Savola S, Gomez A, Moran S, et al. MAX inactivation in small cell lung cancer disrupts MYC-SWI/SNF programs and is synthetic lethal with BRG1. Cancer Discov. 2014;4:292–303.

    Article  CAS  Google Scholar 

  18. Medina PP, Romero OA, Kohno T, Montuenga LM, Pio R, Yokota J, Sanchez-Cespedes M. Frequent BRG1/SMARCA4-inactivating mutations in human lung cancer cell lines. Hum Mutat. 2008;29(5):617–22. doi:10.1002/humu.20730.

    Article  CAS  PubMed  Google Scholar 

  19. Medina PP, Sanchez-Cespedes M. Involvement of the chromatin-remodeling factor BRG1/SMARCA4 in human cancer. Epigenetics. 2008;3(2):64–8.

    Article  Google Scholar 

  20. Medina PP, Carretero J, Ballestar E, Angulo B, Lopez-Rios F, Esteller M, Sanchez-Cespedes M. Transcriptional targets of the chromatin-remodelling factor SMARCA4/BRG1 in lung cancer cells. Hum Mol Genet. 2005;14(7):973–82.

    Article  CAS  Google Scholar 

  21. Medina PP, Carretero J, Fraga MF, Esteller M, Sidransky D, Sanchez-Cespedes M. Genetic and epigenetic screening for gene alterations of the chromatin-remodeling factor, SMARCA4/BRG1, in lung tumors. Genes Chromosomes Cancer. 2004;41(2):170–7.

    Article  CAS  Google Scholar 

  22. Vangamudi B, Paul TA, Shah PK, Kost-Alimova M, Nottebaum L, Shi X, et al. The SMARCA2/4 ATPase domain surpasses the bromodomain as a drug target in SWI/SNF-mutant cancers: insights from cDNA rescue and PFI-3 inhibitor studies. Cancer Res. 2015;75:3865–78.

    Article  CAS  Google Scholar 

  23. Schiaffino-Ortega S, Balinas C, Cuadros M, Medina PP. SWI/SNF proteins as targets in cancer therapy. J Hematol Oncol. 2014;7:81.

    Article  Google Scholar 

  24. Coira IF, Rufino-Palomares EE, Romero OA, Peinado P, Metheetrairut C, Boyero-Corral L, et al. Expression inactivation of SMARCA4by microRNAs in lung tumors. Hum Mol Genet. 2015;24:1400–9.

    Article  CAS  Google Scholar 

  25. Salemi D, Cammarata G, Agueli C, Augugliaro L, Corrado C, Bica MG, et al. miR-155 regulative network in FLT3 mutated acute myeloid leukemia. Leuk Res. 2015;39:883–96.

    Article  CAS  Google Scholar 

  26. Ruffin N, Lévy Y, Swaminathan S. Role of miR-155 in the regulation of lymphocyte immune function and disease. Immunology. 2014;142:32–8.

    Article  Google Scholar 

  27. Den Boer ML. MicroRNAs in acute leukemia: from biological players to clinical contributors. Leukemia. 2012;26:1–12.

    Article  Google Scholar 

  28. Gerloff D, Grundler R, Wurm AA, Bräuer-Hartmann D, Katzerke C, Hartmann JU, et al. NF-κB/STAT5/miR-155 network targets PU.1 in FLT3-ITD-driven acute myeloid leukemia. Leukemia. 2015;3:535–47.

    Article  Google Scholar 

  29. Wang M, Tan LP, Dijkstra MK, van Lom K, Robertus JL, Harms G, et al. miRNA analysis in B cell chronic lymphocytic leukaemia: proliferation centres characterized by low miR-150 and high BIC/miR-155 expression. J Pathol. 2008;215:13–20.

    Article  CAS  Google Scholar 

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    Authors and Affiliations

    1. Department of Biochemistry and Molecular Biology III and Immunology, University of Granada, Granada, Spain

      M. Cuadros, V. Sánchez-Martín, J. Martín-Padrón & L. Boyero

    2. GENYO, Centre for Genomics and Oncological Research, Granada, Spain

      M. Cuadros, V. Sánchez-Martín, A. Herrera, C. Baliñas, J. Martín-Padrón, L. Boyero, P. Peinado & P. P. Medina

    3. Department of Biochemistry and Molecular Biology I, University of Granada, Granada, Spain

      A. Herrera, P. Peinado & P. P. Medina

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    1. M. Cuadros
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    2. V. Sánchez-Martín
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    Correspondence to P. P. Medina.

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    The authors declare that they have no conflict of interest. All data are true and accurate to the knowledge of the authors.

    Research involving human participants and/or animals

    This article does not contain any studies with human participants or animals performed by any of the authors.

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    This article does not contain any studies with human participants performed by any of the authors. Therefore, informed consent is not included.

    Funding

    PM’s lab is funded by the Ministry of Economy of Spain (SAF2015-67919-R), Junta de Andalucía (P12-BIO-1655), the Deutsche José Carreras Leukämie-Stiftung, BBVA Foundation, and Eduardo-Gallego Grant 2015 from Francisco Cobos Foundation and J. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

    Additional information

    M. Cuadros and V. Sánchez-Martín contributed equally to this work.

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    Cuadros, M., Sánchez-Martín, V., Herrera, A. et al. BRG1 regulation by miR-155 in human leukemia and lymphoma cell lines. Clin Transl Oncol 19, 1010–1017 (2017). https://doi.org/10.1007/s12094-017-1633-2

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